International Journal of Medical Sciences

Impact factor

15 December 2018

ISSN 1449-1907 News feeds of published articles

Manuscript login | Account

open access Global reach, higher impact

Journal of Genomics in PubMed Central. Submit manuscript now...


Journal of Cancer

International Journal of Biological Sciences

Journal of Genomics



Journal of Biomedicine

PubMed Central Indexed in Journal Impact Factor

Int J Med Sci 2007; 4(1):36-44. doi:10.7150/ijms.4.36

Research Paper

Proteomic analysis of mechanisms of hypoxia-induced apoptosis in trophoblastic cells

Shin-ichi Ishioka, Yoshiaki Ezaka, Kota Umemura, Takuhiro Hayashi, Toshiaki Endo, Tsuyoshi Saito

Department of Obstetrics and Gynecology, Sapporo Medical University, School of Medicine, Sapporo, Japan


Preeclampsia is often accompanied by hypoxia of the placenta and this condition induces apoptosis in trophoblastic cells. The aim of this study was to characterize global changes of apoptosis-related proteins induced by hypoxia in trophoblastic cells so as to clarify the mechanism of hypoxia-induced apoptosis by using the PoweBlot, an antibody-based Western array. Human choriocarcinoma cell line JAR was cultured for 24 hours under aerobic and hypoxic conditions. Hypoxia induced apoptosis accompanied by increased expression of Bcl-x, Caspase-3 and -9, Hsp70, PTEN, and Bag-1. Bad, pan-JNK/SAPK-1, Bcl-2, Bid, and Caspase-8 showed decreased expression. Hypoxia-induced apoptosis was increased with the transfection of a bag-1 antisense oligonucleotide. The bag-1 antisense oligonucleotide affected the expression of Bid, Bad, Bcl-2, JNK, and phosphorylated JNK, although expression of PTEN and Bcl-X did not change. Bag-1 may inhibit apoptosis by suppressing the expression of Bid and Bad. It may also enhance apoptosis by inhibiting the expression of Bcl-2 and by modulating phosphorylation of JNK. Both mitochondrial and stress-activated apoptosis pathways played important roles in the hypoxia induced cell death of trophoblastic cells. These findings will contribute to establish new approach to detect hypoxic stress of the placenta, which leads to preeclampsia and other hypoxia-related obstetrics complications.

Keywords: Hypoxia, apoptosis, trophoblast, preeclampsia

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
How to cite this article:
Ishioka Si, Ezaka Y, Umemura K, Hayashi T, Endo T, Saito T. Proteomic analysis of mechanisms of hypoxia-induced apoptosis in trophoblastic cells. Int J Med Sci 2007; 4(1):36-44. doi:10.7150/ijms.4.36. Available from